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Lateral beam sizes of the ¹⁵O and ¹¹C ion beams with momentum acceptances of 5% and 0.5% in the x dimension measured with the cross monitor at the wall of the water phantom.
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In heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which off...
Citations
... Concurrently, the possibilities opened by radioactive ion beam (RIB) facilities (Blumenfeld et al 2013) have driven the hadrontherapy community to consider radioactive beams for therapy (Durante and Parodi 2020), with the main consideration so far being the possibility for online diagnoses. Radioactive ions currently under investigation are similar to carbon, such as 10 C, 11 C or 15 O (Augusto et al 2016, Mohammadi et al 2022. Indeed, these ions present a similar relative biological efficiency compared to carbon but will also exhibit the same drawbacks: higher cost and significant fragmentation tail. ...
... Indeed, the produced RIB usually exhibits a higher angular and momentum spread. This can lead to increased uncertainties on the ion range in matter, as highlighted in Mohammadi et al (2020). ...
Purpose:Although hadrontherapy for cancer treatment has grown in popularity these past years, the use of protons and carbon ions for therapy remains debated compared to X-ray therapy. While a biological advantage of protons is not clearly demonstrated, therapy using carbon ions is often criticized for its high cost. Furthermore, the nuclear interactions undergone by carbons inside the patient are responsible for an additional dose delivered after the Bragg peak (BP). Therefore, a renewed interest in lighter ions with higher biological efficiency than protons was recently observed. In this context, helium and lithium ions represent a good compromise between protons and carbons, as they exhibit a higher LET than protons in the Bragg peak and can be accelerated by cyclotrons. The possibility of accelerating radioactive8Li, decaying in 2 α-particles, and8He, decaying in8Li by β- decay, is particularly interesting.Method:This work aims to assess the pertinence of the use of8Li and8He ions for therapy by Monte Carlo simulations carried out with GEANT4.Results:It was calculated that the8Li and8He decay results in an increase of the LET of almost a factor 2 in the BP compared to stable7Li and4He. This also results in a higher dose deposited in the BP without an increase of the dose in the plateau region, and a lower dose after the BP due to fragmentation. It was also shown that both 8He and8Li can have potential interest for prompt-gamma monitoring techniques. Finally, the feasibility of accelerating facilities delivering8Li and8He was also discussed.Conclusion:In this study, we demonstrate that both8Li and8He have interesting properties for therapy. Indeed, simulations predict that8Li and8He are a good compromise between proton and12C, both in terms of LET and dose.
... Shorter half-lives of the RIBs (20.33 min and 19.3 s for 11 C and 10 C, respectively), would reduce the time of PET signal acquisition and make the impact of the biological washout less significant 15 . Finally, the activity peaks would match the mean ranges of the primaries and will be correlated with the R80 of the Bragg peaks (SOBP), i.e., the position in the distal fall-off where the dose drops to 80% of the SOBP value 16 . ...
Sharp dose gradients and high biological effectiveness make ions such as ¹²C an ideal tool to treat deep-seated tumors, however, at the same time, sensitive to errors in the range prediction. Tumor safety margins mitigate these uncertainties, but during the irradiation they lead to unavoidable damage to the surrounding healthy tissue. To fully exploit the Bragg peak benefits, a large effort is put into establishing precise range verification methods. Despite positron emission tomography being widely in use for this purpose in ¹²C therapy, the low count rates, biological washout, and broad activity distribution still limit its precision. Instead, radioactive beams used directly for treatment would yield an improved signal and a closer match with the dose fall-off, potentially enabling precise in vivo beam range monitoring. We have performed a treatment planning study to estimate the possible impact of the reduced range uncertainties, enabled by radioactive ¹¹C ions treatments, on sparing critical organs in tumor proximity. Compared to ¹²C treatments, (i) annihilation maps for ¹¹C ions can reflect sub- millimeter shifts in dose distributions in the patient, (ii) outcomes of treatment planning with ¹¹C significantly improve and (iii) less severe toxicities for serial and parallel critical organs can be expected.
... Shorter half-lives of the RIBs (20.33 min and 19.3 s for 11 C and 10 C, respectively), would reduce the time of PET signal acquisition and make the impact of the biological washout less significant [15]. Finally, the activity peaks would match the mean ranges of the primaries and will be correlated with the R80 of the Bragg peaks (SOBP), i.e., the position in the distal fall-off where the dose drops to 80% of the SOBP value [16]. ...
Radiotherapy with heavy ions, in particular, 12C beams, is one of the most advanced forms of cancer treatment. Sharp dose gradients and high biological effectiveness in the target region make them an ideal tool to treat deep-seated and radioresistant tumors, however, at the same time, sensitive to small errors in the range prediction. Safety margins are added to the tumor volume to mitigate these uncertainties and ensure its uniform coverage, but during the irradiation they lead to unavoidable damage to the surrounding healthy tissue. To fully exploit the benefits of a sharp Bragg peak, a large effort is put into establishing precise range verification methods for the so-called image-guided radiotherapy. Despite positron emission tomography being widely in use for this purpose in 12C ion therapy, the low count rates, biological washout, and broad shape of the activity distribution still limit its precision to a few millimeters. Instead, radioactive beams used directly for treatment would yield an improved signal and a closer match with the dose fall-off, potentially enabling precise in vivo beam range monitoring. We have performed a treatment planning study to estimate the possible impact of the reduced range uncertainties, enabled by radioactive 11C beams treatments, on sparing critical organs in the tumor proximity. We demonstrate that (i) annihilation maps for 11C ions can in principle reflect even millimeter shifts in dose distributions in the patient, (ii) outcomes of treatment planning with 11C beams are significantly improved in terms of meeting the constraints for the organs at risk compared to 12C plans, and (iii) less severe toxicities for serial and parallel critical organs can be expected following 11C treatment with reduced range uncertainties, compared to 12C treatments.
... This, together with the short half-lives of the radioisotopes (20.33 min for 11 C and 19.3 s for 10 C), allows to reduce the time required to collect the PET signal, opening the possibility of an online range monitoring and also reducing the biological washout of the PET signal [14,15]. Additionally, differently than in the case of stable beams, with RIB the activity peak matches the mean ranges 35 of the primaries and is correlated with the 80% distal fall-off after the Bragg peak (and almost coincides with the peak position in case of negligible beam momentum spread) [16]. ...
Owing to the favourable depth-dose distribution and the radiobiological properties of heavy ion radiation, ion beam therapy shows an improved success/toxicity ratio compared to conventional radiotherapy. The sharp dose gradients and very high doses in the Bragg peak region, which represent the larger physical advantage of ion beam therapy, make it also extremely sensitive to range uncertainties. The use of β+-radioactive ion beams would be ideal for simultaneous treatment and accurate online range monitoring through PET imaging. Since all the unfragmented primary ions are potentially contributing to the PET signal, these beams offer an improved image quality while preserving the physical and radiobiological advantages of the stable counterparts. The challenging production of radioactive ion beams and the difficulties in reaching high intensities, have discouraged their clinical application. In this context, the project Biomedical Applications of Radioactive ion Beams (BARB) started at GSI (Helmholtzzentrum für Schwerionenforschung GmbH) with the main goal to assess the technical feasibility and investigate possible advantages of radioactive ion beams on the pre-clinical level. During the first experimental campaign ¹¹C and ¹⁰C beams were produced and isotopically separated with the FRagment Separator (FRS) at GSI. The β+-radioactive ion beams were produced with a beam purity of 99% for all the beam investigated (except one case where it was 94%) and intensities potentially sufficient to treat a small animal tumors within few minutes of irradiation time, ∼106 particle per spill for the ¹⁰C and ∼107 particle per spill for the ¹¹C beam, respectively. The impact of different ion optical parameters on the depth dose distribution was studied with a precision water column system. In this work, the measured depth dose distributions are presented together with results from Monte Carlo simulations using the FLUKA software.
... We have shown feasibility of using in-beam PET to image radioactive ion beams of 11 C and 15 O for direct visualization of beam stopping positions using our OpenPET prototypes (Mohammadi et al , 2019. We have confirmed that the difference between the beam stopping position and the dose peak was smaller than the PET spatial resolution for both beams and the differences depend on the beam momentum spread (Mohammadi et al 2019(Mohammadi et al , 2020. ...
... The back projection approach was applied to the measured data. distance of 2.5 mm can be explained as the difference caused by the energy spread of the 10 C beam (Mohammadi et al 2019(Mohammadi et al , 2020. Iseki et al measured the range of a probing 10 C ion beam with the momentum acceptance of 0.8% at the HIMAC using a positron camera in a 150 mm diameter spherical PMMA phantom within an analysis uncertainty of ±0.3 mm (Iseki et al 2004). ...
Objective. In carbon ion therapy, the visualization of the range of incident particles in a patient body is important for treatment verification. In-beam positron emission tomography (PET) imaging is one of the methods to verify the treatment in ion therapy due to the high quality of PET images. We have shown the feasibility of in-beam PET imaging of radioactive 15O and 11C ion beams for range verification using our OpenPET system. Recently, we developed a whole gamma imager (WGI) that can simultaneously work as PET, single gamma ray and triple gamma ray imaging. The WGI has high potential to detect the location of 10C, which emits positrons with a simultaneous gamma ray of 718 keV, within the patient’s body during ion therapy. Approach. In this work, we focus on investigating the performance of WGI for 10C imaging and its feasibility for range verification in carbon ion therapy. First, the performance of the WGI was studied to image a 10C point source using the Geant4 toolkit. Then, the feasibility of WGI was investigated for an irradiated polymethyl methacrylate (PMMA) phantom with a 10C ion beam at the carbon therapy facility of the Heavy Ion Medical Accelerator in Chiba (HIMAC). Main results. The average spatial resolution and sensitivity for the simulated 10C point source at the centre of the field of view were 5.5 mm FWHM and 0.010%, respectively. The depth dose of the 10C ion beam was measured, and the triple gamma image of 10C nuclides for an irradiated PMMA phantom was obtained by applying a simple back projection to the detected triple gammas. Significance. The shift between Bragg peak position and position of the peak of the triple gamma image in an irradiated PMMA phantom was 2.8±0.8 mm, which demonstrates the capability of triple gamma imaging using WGI for range verification of 10C ion beams.
... Most of these problems are automatically overcome if b +radioactive ion beams (RIB) are directly used for both treatment and imaging. Such radioactive ion beams would improve the count rate by an order of magnitude (26), reduce the shift between measured activity and dose (27), and mitigate the washout blur of the image with short-lived isotopes and inbeam acquisition, eventually leading to sub-mm resolution. Attempts to use RIB in therapy started almost half a century ago during the heavy ion therapy pilot project at the Lawrence Berkeley Laboratory (CA, USA) (28), but they were always hampered by the low intensity of the secondary beams produced by fragmentation of the primary ion used for therapy (29). ...
... The atomic interaction (energy loss, energy-loss straggling and angular straggling) of the ion-beam with the tissue is the dominant physical process involved in the ion-beam therapy, and the accurate understanding of corresponding properties like range and range straggling are of very high practical importance. At HIMAC (Japan), the ranges of various PET isotopes ( 10,11 C, 14,15 O) have been investigated extensively (27,44,45). The range distribution of the selected fragments is primarily determined by the initial energy distribution. ...
Several techniques are under development for image-guidance in particle therapy. Positron (β⁺) emission tomography (PET) is in use since many years, because accelerated ions generate positron-emitting isotopes by nuclear fragmentation in the human body. In heavy ion therapy, a major part of the PET signals is produced by β⁺-emitters generated via projectile fragmentation. A much higher intensity for the PET signal can be obtained using β⁺-radioactive beams directly for treatment. This idea has always been hampered by the low intensity of the secondary beams, produced by fragmentation of the primary, stable beams. With the intensity upgrade of the SIS-18 synchrotron and the isotopic separation with the fragment separator FRS in the FAIR-phase-0 in Darmstadt, it is now possible to reach radioactive ion beams with sufficient intensity to treat a tumor in small animals. This was the motivation of the BARB (Biomedical Applications of Radioactive ion Beams) experiment that is ongoing at GSI in Darmstadt. This paper will present the plans and instruments developed by the BARB collaboration for testing the use of radioactive beams in cancer therapy.
... Even if this shift is smaller than the one observed using stable ions for treatment and projectile fragments for PET imaging (Figure 2), it increases with the momentum acceptance. Recent measurements at HIMAC shows that for 11 C, the shift is around 2 mm at 5% acceptance and is reduced to 0.1 mm at 0.5% momentum acceptance [84]. Momentum spreads can therefore translate in significant range spreads at the site of stopping ( Table 2). ...
Heavy ion therapy can deliver high doses with high precision. However, image guidance is needed to reduce range uncertainty. Radioactive ions are potentially ideal projectiles for radiotherapy because their decay can be used to visualize the beam. Positron-emitting ions that can be visualized with PET imaging were already studied for therapy application during the pilot therapy project at the Lawrence Berkeley Laboratory, and later within the EULIMA EU project, the GSI therapy trial in Germany, MEDICIS at CERN, and at HIMAC in Japan. The results show that radioactive ion beams provide a large improvement in image quality and signal-to-noise ratio compared to stable ions. The main hindrance toward a clinical use of radioactive ions is their challenging production and the low intensities of the beams. New research projects are ongoing in Europe and Japan to assess the advantages of radioactive ion beams for therapy, to develop new detectors, and to build sources of radioactive ions for medical synchrotrons.
Pioneering investigations on the usage of positron-emission-tomography (PET) for the monitoring of ion beam therapy with light (protons, helium) and heavier (stable and radioactive neon, carbon and oxygen) ions started shortly after the first realization of planar and tomographic imaging systems, which were able to visualize the annihilation of positrons resulting from irradiation induced or implanted positron emitting nuclei. And while the first clinical experience was challenged by the utilization of instrumentation directly adapted from nuclear medicine applications, new detectors optimized for this unconventional application of PET imaging are currently entering the phase of (pre)clinical testing for more reliable monitoring of treatment delivery during irradiation. Moreover, recent advances in detector technologies and beam production open several new exciting opportunities which will not only improve the performance of PET imaging under the challenging conditions of in-beam applications in ion beam therapy, but will also likely expand its field of application. In particular, the combination of PET and Compton imaging can enable the most efficient utilization of all possible radiative emissions for both stable and radioactive ion beams, while positronium lifetime imaging may enable probing new features of the underlying tumour and normal tissue environment. Thereby, PET imaging will not only provide means for volumetric reconstruction of the delivered treatment and in-vivo verification of the beam range, but can also shed new insights for biological optimization of the treatment or treatment response assessment.
Sharp dose gradients and high biological effectiveness make heavy ions such as ¹² C an ideal tool to treat deep-seated tumors, however, at the same time, sensitive to errors in the range prediction. Tumor safety margins mitigate these uncertainties, but during the irradiation they lead to unavoidable damage to the surrounding healthy tissue. To fully exploit the Bragg peak benefits, a large effort is put into establishing precise range verification methods. Despite positron emission tomography being widely in use for this purpose in ¹² C therapy, the low count rates, biological washout, and broad activity distribution still limit its precision. Instead, radioactive beams used directly for treatment would yield an improved signal and a closer match with the dose fall-off, potentially enabling precise in vivo beam range monitoring. We have performed a treatment planning study to estimate the possible impact of the reduced range uncertainties, enabled by radioactive ¹¹ C ions treatments, on sparing critical organs in tumor proximity. Compared to ¹² C treatments, (i) annihilation maps for ¹¹ C ions can reflect sub- millimeter shifts in dose distributions in the patient, (ii) outcomes of treatment planning with ¹¹ C significantly improve and (iii) less severe toxicities for serial and parallel critical organs can be expected.
